Frontiers in Immunology (Apr 2023)
Impact of endogenous glucocorticoid on response to immune checkpoint blockade in patients with advanced cancer
- Yu Cui,
- Yu Cui,
- Yu Cui,
- Xinyue Han,
- Xinyue Han,
- Xinyue Han,
- Hongtao Liu,
- Qi Xie,
- Qi Xie,
- Qi Xie,
- Yaping Guan,
- Yaping Guan,
- Yaping Guan,
- Beibei Yin,
- Beibei Yin,
- Beibei Yin,
- Junjuan Xiao,
- Junjuan Xiao,
- Junjuan Xiao,
- Dongfeng Feng,
- Dongfeng Feng,
- Dongfeng Feng,
- Xuan Wang,
- Xuan Wang,
- Xuan Wang,
- Junwei Li,
- Junwei Li,
- Junwei Li,
- Jinghua Chen,
- Jinghua Chen,
- Jinghua Chen,
- Xiaolin Liu,
- Xiaolin Liu,
- Xiaolin Liu,
- Xingyu Li,
- Xingyu Li,
- Xingyu Li,
- Weiwei Nie,
- Weiwei Nie,
- Weiwei Nie,
- Lin Ma,
- Lin Ma,
- Lin Ma,
- Hairong Liu,
- Hairong Liu,
- Hairong Liu,
- Jing Liang,
- Jing Liang,
- Jing Liang,
- Yan Li,
- Yan Li,
- Yan Li,
- Baocheng Wang,
- Jun Wang,
- Jun Wang,
- Jun Wang
Affiliations
- Yu Cui
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Yu Cui
- Shandong Lung Cancer Institute, Jinan, China
- Yu Cui
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Xinyue Han
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Xinyue Han
- Shandong Lung Cancer Institute, Jinan, China
- Xinyue Han
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Hongtao Liu
- Department of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Qi Xie
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Qi Xie
- Shandong Lung Cancer Institute, Jinan, China
- Qi Xie
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Yaping Guan
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Yaping Guan
- Shandong Lung Cancer Institute, Jinan, China
- Yaping Guan
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Beibei Yin
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Beibei Yin
- Shandong Lung Cancer Institute, Jinan, China
- Beibei Yin
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Junjuan Xiao
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Junjuan Xiao
- Shandong Lung Cancer Institute, Jinan, China
- Junjuan Xiao
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Dongfeng Feng
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Dongfeng Feng
- Shandong Lung Cancer Institute, Jinan, China
- Dongfeng Feng
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Xuan Wang
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Xuan Wang
- Shandong Lung Cancer Institute, Jinan, China
- Xuan Wang
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Junwei Li
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Junwei Li
- Shandong Lung Cancer Institute, Jinan, China
- Junwei Li
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Jinghua Chen
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Jinghua Chen
- Shandong Lung Cancer Institute, Jinan, China
- Jinghua Chen
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Xiaolin Liu
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Xiaolin Liu
- Shandong Lung Cancer Institute, Jinan, China
- Xiaolin Liu
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Xingyu Li
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Xingyu Li
- Shandong Lung Cancer Institute, Jinan, China
- Xingyu Li
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Weiwei Nie
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Weiwei Nie
- Shandong Lung Cancer Institute, Jinan, China
- Weiwei Nie
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Lin Ma
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Lin Ma
- Shandong Lung Cancer Institute, Jinan, China
- Lin Ma
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Hairong Liu
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Hairong Liu
- Shandong Lung Cancer Institute, Jinan, China
- Hairong Liu
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Jing Liang
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Jing Liang
- Shandong Lung Cancer Institute, Jinan, China
- Jing Liang
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Yan Li
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Yan Li
- Shandong Lung Cancer Institute, Jinan, China
- Yan Li
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- Baocheng Wang
- Department of Oncology, The 960th Hospital, The PEOPLE’s Liberation Army, Jinan, China
- Jun Wang
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China
- Jun Wang
- Shandong Lung Cancer Institute, Jinan, China
- Jun Wang
- Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China
- DOI
- https://doi.org/10.3389/fimmu.2023.1081790
- Journal volume & issue
-
Vol. 14
Abstract
BackgroundPrevious studies indicate that exogenous use of glucocorticoid (GC) affects immune checkpoint inhibitor (ICI) efficacy. However, there is a paucity of clinical data evaluating the direct impact of endogenous GC on the efficacy for cancer patients with immune checkpoint blockade.MethodsWe first compared the endogenous circulating GC levels in healthy individuals and patients with cancer. We next retrospectively reviewed patients with advanced cancer with PD-1/PD-L1 inhibitor alone or combination therapy in a single center. The effects of baseline circulating GC levels on objective response rate (ORR), durable clinical benefit (DCB), progression‐free survival (PFS), and overall survival (OS) were analyzed. The association of the endogenous GC levels with circulating lymphocytes, cytokines levels, and neutrophil to lymphocyte ratio, and tumor infiltrating immune cells, were systematically analyzed.ResultsThe endogenous GC levels in advanced cancer patients were higher than those in early-stage cancer patients as well as healthy people. In the advanced cancer cohort with immune checkpoint blockade (n=130), patients with high baseline endogenous GC levels (n=80) had a significantly reduced ORR (10.0% vs 40.0%; p<0.0001) and DCB (35.0% vs 73.5%, p=0.001) compared to those with low endogenous GC levels (n=50). The increased GC levels was significantly associated with reduced PFS (HR 2.023; p=0.0008) and OS (HR 2.809; p=0.0005). Moreover, statistically significant differences regarding PFS, and OS were also detected after propensity score matching. In a multivariable model, the endogenous GC was identified as an independent indicator for predicting PFS (HR 1.779; p=0.012) and OS (HR 2.468; p=0.013). High endogenous GC levels were significantly associated with reduced lymphocytes (p=0.019), increased neutrophil to lymphocyte ratio (p=0.0009), and increased interleukin-6 levels (p=0.025). Patients with high levels of endogenous GC had low numbers of tumor infiltrating CD3+ (p=0.001), CD8+ T (p=0.059), and CD4+ T (p=0.002) cells, and the numbers of circulating PD-1+ NK cells (p=0.012), and the ratio of CD8+PD-1+ to CD4+PD-1+ (p=0.031) were higher in patients with high levels of endogenous GC compared to low levels of endogenous GC.ConclusionBaseline endogenous GC increase executes a comprehensive negative effect on immunosurveillance and response to immunotherapy in real-world cancer patients accompanied with cancer progression.
Keywords
- glucocorticoid
- programmed cell death protein-1
- programmed cell death ligand-1
- immune checkpoint inhibitor
- advanced cancer